9-137615202-G-C

Variant names:

• chr9-137615202-G-C
• rs59628511
• NM_152285.4:c.*64G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_152285.4(ARRDC1):​c.*64G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ARRDC1 NM_152285.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.42
• Publications: 2 publications found

Genes affected

ARRDC1 (HGNC:28633): (arrestin domain containing 1) Enables several functions, including arrestin family protein binding activity; ubiquitin ligase-substrate adaptor activity; and ubiquitin protein ligase binding activity. Involved in several processes, including cellular protein metabolic process; extracellular vesicle biogenesis; and negative regulation of Notch signaling pathway. Located in cytoplasmic vesicle; extracellular vesicle; and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000283411 (HGNC:):

ARRDC1-AS1 (HGNC:23395): (ARRDC1 antisense RNA 1) This transcribed locus is thought to be non-coding. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jun 2014]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.41).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARRDC1	NM_152285.4	c.*64G>C		3_prime_UTR_variant	Exon 8 of 8	ENST00000371421.9	NP_689498.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARRDC1	ENST00000371421.9	c.*64G>C		3_prime_UTR_variant	Exon 8 of 8	1	NM_152285.4	ENSP00000360475.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1270326 Hom.: 0 Cov.: 22 AF XY: 0.00 AC XY: 0 AN XY: 620970

African (AFR) AF: 0.00 AC: 0 AN: 27762

American (AMR) AF: 0.00 AC: 0 AN: 22870

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18808

East Asian (EAS) AF: 0.00 AC: 0 AN: 35232

South Asian (SAS) AF: 0.00 AC: 0 AN: 64948

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 36796

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4944

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1006170

Other (OTH) AF: 0.00 AC: 0 AN: 52796

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.41
CADD	Benign	13
DANN	Benign	0.86
PhyloP100		1.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs59628511; hg19: chr9-140509654;